Divergence of bacterial lipopolysaccharide pro-apoptotic signaling downstream of IRAK-1

被引:55
作者
Bannerman, DD
Tupper, JC
Erwert, RD
Winn, RK
Harlan, JM
机构
[1] Univ Washington, Sch Med, Div Hematol, Dept Surg, Seattle, WA 98104 USA
[2] Univ Washington, Sch Med, Dept Med, Seattle, WA 98104 USA
[3] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA
关键词
D O I
10.1074/jbc.M111249200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The vascular endothelium is a key target of circulating bacterial lipopolysaccharide (LPS). LPS elicits a wide array of endothelial responses, including the up-regulation of cytokines, adhesion molecules, and tissue factor, many of which are dependent on NF-kappaB activation. In addition, LPS has been demonstrated to induce endothelial apoptosis both in vitro and in vivo. Although the mechanism by which LPS activates NF-kappaB has been well elucidated, the signaling pathway(s) involved in LPS-induced apoptosis remains unknown. Using a variety of dominant negative constructs, we have identified a role for MyD88 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in mediating LPS pro-apoptotic signaling in human endothelial cells. We also demonstrate that LPS-induced endothelial NF-kappaB activation and apoptosis occur independent of one another. Together, these data suggest that the proximal signaling molecules involved in LPS-induced NF-kappaB activation have a requisite involvement in LPS-induced apoptosis and that the pathways leading to NF-kappaB activation and apoptosis diverge downstream of IRAK-1.
引用
收藏
页码:8048 / 8053
页数:6
相关论文
共 59 条
[1]   HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE [J].
ADES, EW ;
CANDAL, FJ ;
SWERLICK, RA ;
GEORGE, VG ;
SUMMERS, S ;
BOSSE, DC ;
LAWLEY, TJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) :683-690
[2]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[3]   The apoptotic signaling pathway activated by Toll-like receptor-2 [J].
Aliprantis, AO ;
Yang, RB ;
Weiss, DS ;
Godowski, P ;
Zychlinsky, A .
EMBO JOURNAL, 2000, 19 (13) :3325-3336
[4]  
Bannerman DD, 1999, LAB INVEST, V79, P1181
[5]   A constitutive cytoprotective pathway protects endothelial cells from lipopolysaccharide-induced apoptosis [J].
Bannerman, DD ;
Tupper, JC ;
Ricketts, WA ;
Bennett, CF ;
Winn, RK ;
Harlan, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (18) :14924-14932
[6]   Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins [J].
Bannerman, DD ;
Sathyamoorthy, M ;
Goldblum, SE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (52) :35371-35380
[7]   Interleukin 20: Discovery, receptor identification, and role in epidermal function [J].
Blumberg, H ;
Conklin, D ;
Xu, WF ;
Grossmann, A ;
Brender, T ;
Carollo, S ;
Eagan, M ;
Foster, D ;
Haldeman, BA ;
Hammond, A ;
Haugen, H ;
Jelinek, L ;
Kelly, JD ;
Madden, K ;
Maurer, MF ;
Parrish-Novak, J ;
Prunkard, D ;
Sexson, S ;
Sprecher, C ;
Waggie, K ;
West, J ;
Whitmore, TE ;
Yao, L ;
Kuechle, MK ;
Dale, BA ;
Chandrasekher, YA .
CELL, 2001, 104 (01) :9-19
[8]   TRAIL receptor-2 signals apoptosis through FADD and caspase-8 [J].
Bodmer, JL ;
Holler, N ;
Reynard, S ;
Vinciguerra, P ;
Schneider, P ;
Juo, P ;
Blenis, J ;
Tschopp, J .
NATURE CELL BIOLOGY, 2000, 2 (04) :241-243
[9]   PLASMA ENDOTOXIN AS A PREDICTOR OF MULTIPLE ORGAN FAILURE AND DEATH IN SYSTEMIC MENINGOCOCCAL DISEASE [J].
BRANDTZAEG, P ;
KIERULF, P ;
GAUSTAD, P ;
SKULBERG, A ;
BRUUN, JN ;
HALVORSEN, S ;
SORENSEN, E .
JOURNAL OF INFECTIOUS DISEASES, 1989, 159 (02) :195-204
[10]   FADD, A NOVEL DEATH DOMAIN-CONTAINING PROTEIN, INTERACTS WITH THE DEATH DOMAIN OF FAS AND INITIATES APOPTOSIS [J].
CHINNAIYAN, AM ;
OROURKE, K ;
TEWARI, M ;
DIXIT, VM .
CELL, 1995, 81 (04) :505-512